This award is funded under the American Recovery and Reinvestment Act of 2009 (Public Law 111-5)."
Designing materials with cues to induce or enhance adult stem cell differentiation into cartilage cells would improve treatment options for patients suffering from osteoarthritis, a degenerative disease that affects articular cartilage. Healthy cartilage protects load-bearing bones and serves as a lubricant for moving joint surfaces but once damaged, cartilage has a limited regenerative potential. There is increasing interest in developing tissue engineered cartilage replacements using adult stem cells seeded on a scaffold. These cells are often differentiated in vitro using soluble growth factors and chemical compounds. Some of the drawbacks of this method include the extensive cell culture time, the use of super-physiological concentrations of growth factors, and the difficulty in maintaining the articular cartilage phenotype and preventing cartilage hypertrophy. Development of materials that incorporate cues for targeted cell differentiation could circumvent these issues and have the added benefit of facilitating the design and construction of a complex three-dimensional tissue.
Intellectual Merit The proposed work will investigate peptide sequences that are derived from chondrogenic growth factors and have been shown to elicit activity in other biological systems. The objectives of this work are to 1) evaluate soluble peptides for their ability to induce or promote mesenchymal stem cell differentiation into cartilage cells, 2) investigate synergistic effects and maintenance of the cartilage phenotype using experimental design techniques, and 3) develop a novel protein-based scaffold and demonstrate the activity of these peptides within the context of a three-dimensional scaffold. The results from this proposal will demonstrate proof of principle and serve as preliminary data for a future NSF proposal that establishes the peptides as a general design rule by systematically examining them in the context of different scaffolds. The future proposal will also explore the interactions of biochemical and biomechanical properties in controlling cell differentiation. In addition, the work proposed here will demonstrate the utility of a new resilin-based protein scaffold containing chemical and photocrosslinking sites. These results will serve as the preliminary data for a separate proposal that investigates the biocompatibility, mechanical properties, and in vivo use for cartilage engineering applications.
Broader Impact The proposed work will improve technologies for treating cartilage damaged from disease or injury. In addition, the methodology developed here can be extended for use in other applications such as bone or soft tissue grafts and for the design of multicellular tissues such the liver or vascularized organs. The PI is committed to the recruitment and retention of underrepresented groups in engineering and will engage in individual and group mentoring of female students (high school, undergraduate, and graduate). As part of the Women in Engineering Program, she is actively involved with the graduate mentoring program and is developing a laboratory module to introduce high school students to a high-throughput technique used to evaluate tissue engineering scaffolds. Undergraduate students from underrepresented groups will be recruited through the Louis Stokes Alliance for Minority Participation (LSAMP) Indiana to participate in research during the summer and academic year. The work will also train a female graduate student and mentor her through the process of obtaining a faculty position where she will serve as a role model and mentor to future students. The research will be integrated into the development of undergraduate and graduate level courses on tissue engineering and protein engineering. These courses will emphasize critical analysis and introduce students to cutting edge technologies through the use of primary literature papers.
